ArticleMolecular therapy. Nucleic acids2019
Suppression of Choroidal Neovascularization and Fibrosis by a Novel RNAi Therapeutic Agent against (Pro)renin Receptor.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Identifying Choroidal Neovascularization-Associated Genes with GenePlexus in a Protein-Protein Interaction Network.Life (Basel, Switzerland) · 2026Article
- An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and Fibrosis.Investigative ophthalmology & visual science · 2026Article
- Spatial transcriptomics reveals regionally altered gene expression that drives retinal degeneration.Communications biology · 2025Article
- Intracellular Signaling Pathways and Their Potential Targeting for Treatment of Ocular Posterior Segment Fibrosis.Journal of ophthalmic & vision research · 2025Review
- Involvement ofBiomedicines · 2024Article
- METTL3-mediated m6A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition.Journal of molecular cell biology · 2023Article
- Potential therapeutic targets for age-related macular degeneration: The nuclear option.Progress in retinal and eye research · 2023Review
- Peptidyl arginine deiminase 4 deficiency protects against subretinal fibrosis by inhibiting Müller glial hypercitrullination.Journal of neuroscience research · 2023Article
- Suppression of myeloid PFKFB3-driven glycolysis protects mice from choroidal neovascularization.British journal of pharmacology · 2022Article
- NURR1 expression regulates retinal pigment epithelial-mesenchymal transition and age-related macular degeneration phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Subretinal fibrosis in neovascular age-related macular degeneration: current concepts, therapeutic avenues, and future perspectives.Cell and tissue research · 2022Review
- Article
- Soluble very low-density lipoprotein receptor (sVLDLR) inhibits fibrosis in neovascular age-related macular degeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Morphologic and Microvascular Differences Between Macular Neovascularization With and Without Subretinal Fibrosis.Translational vision science & technology · 2021Article
- Receptor-Associated Prorenin System in the Trabecular Meshwork of Patients with Primary Open-Angle Glaucoma and Neovascular Glaucoma.Journal of clinical medicine · 2020Article
- Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice.Journal of clinical medicine · 2020Article
- The Role of Inflammation in Age-Related Macular Degeneration.International journal of biological sciences · 2020Review
- Downregulation of AlphaB-crystallin in Retinal Pigment Epithelial Cells Exposed to Diabetes-related StimuliIn vivo (Athens, Greece)Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor-associated prorenin system refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent signaling, and its activation contributes to the molecular pathogenesis of various ocular diseases. We recently developed a new single-stranded RNAi agent targeting both human and mouse (P)RR ((P)RR-proline-modified short hairpin RNA [(P)RR-PshRNA]), and confirmed its therapeutic effect on murine models of ocular inflammation. Here, we investigated the efficacy of (P)RR-PshRNA against laser-induced choroidal neovascularization (CNV) and subretinal fibrosis, both of which are involved in the pathogenesis of age-related macular degeneration (AMD). Administration of (P)RR-PshRNA in mice significantly reduced CNV formation, together with the expression of inflammatory molecules, macrophage infiltration, and extracellular signal-regulated kinase (ERK) 1/2 activation. In addition, (P)RR-PshRNA attenuated subretinal fibrosis, together with epithelial-mesenchymal transition (EMT)-related markers including phosphorylated SMAD2. The suppressive effect of (P)RR-PshRNA is comparable with aflibercept, an anti-vascular endothelial growth factor drug widely used for AMD therapy. AMD patient specimens demonstrated (P)RR co-localization with phosphorylated ERK1/2 in neovascular endothelial cells and retinal pigment epithelial cells. These results indicate that (P)RR contributes to the ocular pathogenesis of both inflammation-related angiogenesis and EMT-driven fibrosis, and that (P)RR-PshRNA is a promising therapeutic agent for AMD.
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